We seek to characterize the fast internal dynamics of proteins and to determine whether these dynamics are relevant to function. The proposed studies will be carried out in the context of two model systems: ubiquitin and the calmodulin complexes. Both of these proteins are of vital importance in eukaryotic biology and are at the same time effectively perfect models for the studies proposed. Because of its size, stability and NMR performance, ubiquitin provides an ideal system with which to comprehensively probe the nature of fast protein dynamics. Calmodulin and its complexes will be used to probe for correlations between dynamics and function, especially in the context of allosteric or cooperative interactions involving residual protein entropy. The dynamics will be monitored by a variety of NMR-based methods, including classical relaxation, CPMG-type dispersion methods, averaging effects in J-coupling and residual dipolar couplings, and hydrogen exchange. This will allow an unusually comprehensive view of protein dynamics to be obtained. Variation in temperature and pressure will allow the energetics and physical nature of the underlying motions to be better understood. In conjunction with several interpretative models, these measures of dynamics will be used to provide a semi-quantitative interpretation of the entropy that they represent. The role of protein entropy in the interaction of calmodulin with target domains will be extensively delineated and compared to existing thermodynamic and structural information about these complexes. Overall, the studies to be carried out will provide a detailed insight into not only the physical nature of fast protein dynamics but also their role in protein function. Understanding the degree to which dynamics and protein entropy participates in fundamental biochemical functions like cooperative ligand binding is critically important to a general understanding of protein structure, folding, stability, dynamics and function.